Bioactive Silver Phosphate/Polyindole Nanocomposites

Materials capable of releasing reactive oxygen species (ROS) can display antibacterial and anticancer activity, and may also have anti-oxidant capacity if they suppress intracellular ROS (e.g. nitric oxide, NO) resulting in anti-inflammatory activity. Herein we report silver phosphate (Ag3PO4)/polyindole (Pln) nanocomposites which display antibacterial, anticancer and anti-inflammatory activity, and have therefore potential for a variety of biomedical applications

Discovery of a gatekeeper residue in the C terminal tail of the extracellular signal-regulated protein kinase 5 (ERK5)

The extracellular signal-regulated protein kinase 5 (ERK5) is a non-redundant mitogen-activated protein kinase (MAPK) that exhibits a unique C terminal extension which comprises distinct structural and functional properties. Here, we sought to elucidate the significance of phosphoacceptor sites in the C terminal transactivation domain of ERK5. We have found that Thr732 acted as a functional gatekeeper residue controlling C terminal-mediated nuclear translocation and transcriptional enhancement. Consistently, using a non-bias quantitative mass spectrometry approach, we demonstrated that phosphorylation at Thr732 conferred selectivity for binding interactions of ERK5 with proteins related to chromatin and RNA biology, whereas a number of metabolic regulators were associated with full-length wild type ERK5. Additionally, our proteomic analysis revealed that phosphorylation of the Ser730-Glu-Thr732-Pro motif could occur independently of dual phosphorylation at Thr218-Glu-Tyr220 in the activation loop. Together these results firmly establish the significance of C terminal phosphorylation in regulating ERK5 function, independently of MEK5. This novel mechanism may be of particular relevance in cancer cells where ERK5 has be found to be hyperphosphoryated on its C terminal tail

Dynamic segmental kinematics of the lumbar spine during diagnostic movements

Background:In vivo measurements of segmental-level kinematics are a promising avenue for better understanding the relationship between pain and its underlying, multi-factorial basis. To date, the bulk of the reported segmental-level motion has been restricted to single plane motions.Methods: The present work implemented a novel marker set used with an optical motion capture system to non-invasively measure dynamic, 3D in vivo segmental kinematics of the lower spine in a laboratory setting. Lumbar spinal kinematics were measured for 28 subjects during 17 diagnostic movements.Results: Overall regional range of motion data and lumbar angular velocity measurement were consistent with previously published studies. Key findings from the work included measurement of differences in ascending versus descending segmental velocities during functional movements and observations of motion coupling paradigms in the lumbar spinal segments.Conclusion: The work contributes to the task of establishing a baseline of segmental lumbar movement patterns in an asymptomatic cohort, which serves as a necessary pre-requisite for identifying pathological and symptomatic deviations from the baseline

Epithelialization of hydrogels achieved by amine functionalization and co-culture with stromal cells

The aim of this study was to develop a hydrogel which would be suitable for corneal cell re-epithelialization when used as a corneal implant. To achieve this, a series of hydrogels were functionalized with primary amines by post-polymerization reactions between amine compounds and glycidyl ether groups attached to the hydrogels. We report a strong correlation between the structure of the amine and the viability of stromal cells and epithelial cells cultured on these hydrogels. Subsequent co-culture of epithelial and stromal cells on the amine modified hydrogels allowed successful expansion of epithelial cells on surfaces functionalized with alkyl α–ω diamines with carbon chain lengths of between 3 and 6. Analysis of variance showed that corneal epithelial cells had a strong preference for surfaces functionalized by the reaction of excess 1,3 diaminopropane with units of glycidyl methacrylate compared to the reaction products of other amines (ammonia; 1,2-diaminoethane; 1,4-diaminobutane or 1,6-diaminohexane). We suggest this approach of amine functionalization combined with stromal/epithelial co-culture offers a promising new approach to achieving a secure corneal epithelium. Keywords: Epithelial cell

Incidence and consequence of acute kidney injury in unselected emergency admissions to a large acute UK hospital trust

BACKGROUND: AKI is common among hospital in-patients and places a huge financial burden on the UK National Health Service, causing increased length of hospital stay and use of critical care services, with increased requirement for complex interventions including dialysis. This may account for up to 0.6% of the total Health Service budget. To investigate the incidence and consequences of AKI, all unselected emergency admissions to a large acute UK single centre University Teaching Hospital over two separate 7 day periods were reviewed. METHODS: A retrospective audit of 745 case records was undertaken (54.6% male) including laboratory data post-discharge or death, with classification of AKI by RIFLE, AKIN and AKIB criteria. Participants were included whether admitted via their general practitioners, the emergency department, or as tertiary specialty transfers. Outcome measures were presence or absence of AKI recorded using each of the three AKI criteria, length of hospital stay (LOS), admission to, and LOS in critical care, and mortality. The most severe grade of AKI only, at any time during the admission, was recorded to prevent double counting. Renal outcome was determined by requirement for renal replacement therapy (RRT), and whether those receiving RRT remained dialysis dependent or not. RESULTS: AKI incidence was 25.4% overall. With approximately one third present on admission and two thirds developing post admission. The AKI group had LOS almost three times higher than the non AKI group (10 vs 4 days). Requirement for critical care beds was 8.1% in the AKI group compared to 1.7% in non AKI group. Overall mortality was 5.5%, with the AKI group at 11.4% versus 3.3% in the non AKI group. CONCLUSIONS: AKI in acute unselected hospital admissions is more common than existing literature suggests, affecting 25% of unselected admissions. In many this is relatively mild and may resolve spontaneously, but is associated with increased LOS, likelihood of admission to critical care, and risk of death. If targeted effective interventions can be developed it seems likely that substantial clinical benefits for the patient, as well as financial and structural benefits for the healthcare organisation may accrue

Oncogenic ERRB2 signals through the AP-1 transcription factor to control mesenchymal-like properties of oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) is a deadly disease with poor survival statistics and few targeted therapies available. One of the most common molecular aberrations in OAC is amplification or activation of the gene encoding the receptor tyrosine kinase ERBB2, and ERBB2 is targeted in the clinic for this subset of patients. However, the downstream consequences of these ERBB2 activating events are not well understood. Here we used a combination of phosphoproteomics, open chromatin profiling and transcriptome analysis on cell line models and patient-derived datasets to interrogate the molecular pathways operating downstream from ERBB2. Integrated analysis of these data sets converge on a model where dysregulated ERBB2 signalling is mediated at the transcriptional level by the transcription factor AP-1. AP-1 in turn controls cell behaviour by acting on cohorts of genes that regulate cell migration and adhesion, features often associated with EMT. Our study therefore provides a valuable resource for the cancer cell signalling community and reveals novel molecular determinants underlying the dysregulated behaviour of OAC cells

Measuring digital health participation in people with intellectual disabilities

Background and proposed aims: People with intellectual disabilities experience greater digital exclusion and have poorer health literacy. In the absence of good quality research, health inequalities are likely to worsen leading to poorer health outcomes. Research is needed to better understand digital health participation in people with intellectual disabilities. Due to low methodological quality of existing measures, assessment of intervention efficacy is difficult. The aim of this research is to co-create a digital health participation scale for people with intellectual disabilities and a proxy measure for carers. Proposed methods: To develop a valid and reliable measure of digital health participation a thematic analysis and synthesis of findings from a scoping review of extant measures and 12 focus groups with 40 people with intellectual disabilities and 20 carers will be conducted. Stages of scale development will include: (i) item generation; (ii) adaptations to the measure; (iii) piloting and seeking consensus; and (iv) psychometric analysis. Preliminary Findings: Based on preliminary reading and discussion this measure of digital health participation will comprise: (i) Digital participation; (ii) Support for digital participation; (iii) Health literacy; (iv) Frequency and success of engagement in digital health activity; (v) Additional inductively derived aspects of digital health participation. Potential implications and applications: The measure will be used in a large scale survey to determine levels of digital health participation and inequality among adults with intellectual disabilities. This will subsequently be used to co-develop guidance and interventions to enhance digital health participation.<br/